JP2008509210A5 - - Google Patents

Claims (16)

The following general formula (I):

[Where
X is -CO-Y- (R ¹ ) _n or SO ₂ -Y- (R ¹ ) _n ;
Y is a cycloalkyl or polycycloalkyl group; or Y is a cycloalkenyl or polycycloalkenyl group;
Each R ¹ is independently selected from a hydrogen atom and an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino group of 1 to 20 carbon atoms;
Alternatively, each R ¹ is independently selected from fluoro, chloro, bromo, iodo, hydroxy, oxyalkyl, amino, aminoalkyl and aminodialkyl groups; and
n is any integer from 1 to m, where m is the maximum number of substituents allowed on the cyclo group Y;
Alternatively, R ¹ is selected from peptide groups having 1 to 4 peptide moieties joined by peptide bonds. ]
The pharmaceutical composition for treating an inflammatory disease containing the compound represented by these, or its pharmaceutically acceptable salt. The following formula (I '):

[Wherein X has the same meaning as described above. ]
The pharmaceutical composition for treating an inflammatory disease containing the compound represented by these . As an active ingredient, the following formula (I):

[Where
X is -CO-Y- (R ¹ ) _n or SO ₂ -Y- (R ¹ ) _n ;
Y is a cycloalkyl or polycycloalkyl group; or Y is a cycloalkenyl or polycycloalkenyl group;
Each R ¹ is independently selected from a hydrogen atom and an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino group of 1 to 20 carbon atoms;
Alternatively, each R ¹ is independently selected from fluoro, chloro, bromo, iodo, hydroxy, oxyalkyl, amino, aminoalkyl and aminodialkyl groups; and
n is any integer from 1 to m, where m is the maximum number of substituents allowed on the cyclo group Y;
Alternatively, R ¹ is selected from peptide groups having 1 to 4 peptide moieties joined by peptide bonds. ]
Or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient and / or carrier. As an active ingredient, the following formula (I ′):

[Wherein X has the same meaning as described above. ]
Or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier and / or excipient. Formula (I) below

[Where
X is -CO-Y- (R ¹ ) _n or SO ₂ -Y- (R ¹ ) _n ;
Y is a cycloalkyl or polycycloalkyl group; or Y is a cycloalkenyl or polycycloalkenyl group;
Each R ¹ is independently selected from a hydrogen atom and an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino group of 1 to 20 carbon atoms;
Alternatively, each R ¹ is independently selected from fluoro, chloro, bromo, iodo, hydroxy, oxyalkyl, amino, aminoalkyl and aminodialkyl groups; and
n is any integer from 1 to m, where m is the maximum number of substituents allowed on the cyclo group Y;
Alternatively, R ¹ is selected from peptide groups having 1 to 4 peptide moieties joined by peptide bonds. ]
Or a pharmaceutically acceptable salt thereof . The following general formula (I '):

[X has the same meaning as above. ]
Or a pharmaceutically acceptable salt thereof . 7. The compound of claim 5 or 6 , or a pharmaceutically acceptable salt thereof, wherein the ring or rings of Y constrain the bond angle of the α-carbon atom to an essentially tetrahedral form (ie, SP ³ hybrid bond). Salt . Less than:
(S) -3- (Cyclohexanecarbonyl) amino-caprolactam;
(S) -3- (1'-methylcyclohexanecarbonyl) amino-caprolactam;
(S) -3- (Cyclohexe-1'-enecarbonyl) amino-caprolactam;
(S) -3- (trans-4'-pentylcyclohexene-1-carbonyl) amino-caprolactam;
(S) -3- (4'-pentyl [2,2,2] bicyclo-octane-1-carbonyl) amino-caprolactam;
(S) -3- (1'-adamantanecarbonyl) amino-caprolactam;
(S) -3- (1'-adamantanylmethanecarbonyl) amino-caprolactam;
(S) -3- (3'-Chloro-1'-adamantanecarbonyl) amino-caprolactam;
(S) -3- (3 ′, 5′-dimethyl-1′-adamantanecarbonyl) amino-caprolactam;
(S) -3- (3 ′, 5 ′, 7′-trimethyl-1′-adamantanecarbonyl) amino-caprolactam;
6. The compound of claim 5, selected from the group consisting of: and sulfonyl analogs thereof; and pharmaceutically acceptable salts thereof.   6. The compound according to claim 5, which is (S) -3- (1'-adamantanecarbonyl) amino-caprolactam or a pharmaceutically acceptable salt thereof. Anti of a compound according to any one of claims 5-9 - including inflammatory amount (arbitrary including reverse inflammatory response to drug) treatment of the symptoms of inflammatory diseases, a pharmaceutical composition for the alleviation or prevention there are, Ru is administered to a patient, said composition. The compound or a pharmaceutically acceptable salt thereof according to claim 5 or 6 , wherein the substituent R ¹ is not a linear alkyl group. The compound according to claim 5 or 6 , or a pharmaceutically acceptable salt thereof, wherein the substituent R ¹ is a branched alkyl group. The compound or pharmaceutically acceptable salt thereof according to claim 5 or 6 , wherein the substituent R ¹ is not an alkyl group. A pharmaceutical composition comprising the compound according to any one of claims 5 to 9 and 11 to 13, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient and / or carrier. . Inflammatory disease comprising the compound according to any one of claims 5 to 9 and 11 to 13, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient and / or carrier. A pharmaceutical composition for treating Said inflammatory disease is autoimmune disease, vascular disease, viral infection or replication, asthma, osteoporosis (low bone density), tumor growth, rheumatoid arthritis, organ transplant rejection and / or delayed graft or organ function, TNF-α level Diseases characterized by elevated levels of disease, psoriasis, skin damage, diseases caused by intracellular parasites, allergies, Alzheimer's disease, antigen-induced regenerative reaction, immune response suppression, multiple sclerosis, ALS, fibrosis and adhesion formation The pharmaceutical composition according to any one of claims 1, 2, 10 and 15 , which is selected from the group.